Summary
Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results
in large clinical trials. Laboratory monitoring is not needed but the effects on common
coagulation assays are incompletely known. Dabigatran was added to plasma from healthy
subjects in the concentration range 0–1,000 μg/l and analysed using several reagents
for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin,
and activated protein C resistance. Typical trough concentrations are about 50 μg/l,
peak concentrations 100–300 μg/l. At 100 μg/l all APTT-results were prolonged. The
concentration required to double APTT ranged between 227 and 286 μg/l, the responses
for all five reagents were similar. PT-reagents were much less affected with almost
no samples above INR 1.2 at 100 μg/l. The effect was sample dilution dependent with
PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran
has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing
or accumulation of dabigatran should be considered. Two of four fibrinogen reagents
underestimated the fibrinogen concentration considerably at expected peak concentration.
Methods based on inhibition of thrombin over-estimated the antithrombin concentration,
but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may
lead to miss-classification of factor V Leiden patients as being normal. Different
coagulation assays, and even different reagents within an assay group, display variable
effects at therapeutic concentrations of dabigatran. Some of these assay variations
are of clinical importance, thus knowledge is needed for a correct interpretation
of results.
Keywords
Dabigatran - thrombin inhibitor - interference - anticoagulant - coagulation assays
